The overall goal of this competing renewal SPORE in skin Cancer from The University of Texas M.D. Anderson Cancer Center is to facilitate innovative translational research in the prevention, detection and treatment of melanoma leading to the elimination of the disease. This SPORE aims to achieve this goal by assembling a talented group of scientists who are committed to the translation of melanoma-specific findings from the laboratory to the clinic as well as from the clinic to the laboratory. The University of Texas M.D. Anderson Cancer Center has prioritized the elimination of melanoma as a health risk, and to this end established in 1998, a Multidisciplinary Research Program in Melanoma to support training and research across traditional administrative boundaries. The program provided resources and a structure that led to our successful funding in 2004 for the first SPORE dedicated entirely to Melanoma, which allowed us to further advance along several translational themes and provide a basis for this renewal application. This SPORE in Melanoma proposes five translational projects, four of which included treatment protocols to begin in successive years and takes advantage of our large melanoma patient population. The five projects and four protocols are served by three cores: Administrative (A), Informatics, Tissue Resource, and Pathology (B), and Biostatics and Bioinformatics (C). The Developmental Research Program (DRP) and Career Development Program (CDP) continue as successful aspects of our SPORE as each new project incorporates at least one DRP/CDP awardee as a new Co-Leader. The five proposed projects address activation of Toll-Like Receptors (TLR) for specific immune stimulation (#1); inhibition of pSTAT3 for control of melanoma metastasis focused in the CNS (#2); elucidation of melanoma JNOS-related inflammation for development of a prognostic signature as well as a target therapy (#3); systemic deliver of angiogenesis inhibitors using nanoliposomal technology (#4); and genetic mechanisms of immunity and inflammation to generate an integrated risk model as part of a population based project (#5). Through this research program and with the full support of The University of Texas M.D. Anderson Cancer Center, this SPORE aims to make a significant impact toward the prevention, detection, and treatment of melanoma in patients.